The purpose of the immune system is to protect the body from potentially harmful substances (antigens) such as microorganisms, toxins, cancer cells, and foreign blood or tissues from another person or species. Antigens are destroyed by the immune response, which includes production of antibodies (molecules that attach to the antigen and make it more susceptible to destruction) and sensitized lymphocytes (specialized white blood cells that recognize and destroy particular antigens).
Immune system disorders occur when the immune response is inappropriate, excessive, or lacking. Autoimmune disorders refers to any disease characterized by abnormal functioning of the immune system that causes the immune system to produce antibodies against its own tissues. This is caused by a hypersensitivity reaction where the immune system reacts to substances that it normally would ignore, i.e. normal “self” body tissues.
Normally, the immune system is capable of differentiating “self” from “non-self” tissue. Some immune system cells (lymphocytes) become sensitized against “self” tissue cells, but these faulty lymphocytes are usually controlled (suppressed) by other lymphocytes. Autoimmune disorders occur when the normal control process is disrupted, or if normal body tissue is altered so that it is no longer recognized as “self.”
Autoimmune disorders typically result in destruction of one or more types of body tissues, abnormal growth of an organ, or changes in organ function. The disorder may affect only one organ or tissue type or may affect multiple organs and tissues. Organs and tissues commonly affected by autoimmune disorders include blood components such as red blood cells, blood vessels, connective tissues, endocrine glands such as the thyroid or pancreas, organs such as the kidney or liver, muscles, joints, and skin.
Examples of autoimmune or autoimmune-related disorders include: Hashimoto's thyroiditis, pernicious anemia, Addison's disease, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, drug-induced lupus erythematosus, multiple scleroris, myasthenia gravis, Reiter's syndrome and Grave's disease.
Symptoms of autoimmune diseases vary widely depending on the type of disease. However, autoimmune diseases are often associated with non-specific symptoms such as fatigue, dizziness, malaise (non-specific feeling of not being well), fever, and low-grade temperature elevations.
Specific autoimmune disease results in the destruction of an organ or tissue resulting in decreased functioning of an organ or tissue (for example, the islet cells of the pancreas are destroyed in diabetes), and/or an increase in size of an organ or tissue (for example, thyroid enlargement in Grave's disease). Symptoms vary depending on the specific disorder and the organ or tissue affected.
Autoimmunity is controlled through balanced suppression of the immune system. The aim is to reduce the immune response against normal body tissue whilst leaving intact the immune response against micro-organisms and abnormal tissues. Clinical treatments for autoimmune diseases typically involve the use of corticosteroids and immunosuppressants (including cyclophosphamide or azathioprine) which reduce the immune response. However, many of treatments available to date are associated with severe adverse side effects.
The present invention seeks to provide alternative therapeutic methods for treating autoimmune diseases which ideally are capable of reducing symptoms and controlling the autoimmune process, whilst maintaining the ability to fight disease. More particularly, the invention relates to the treatment of diseases associated with antinuclear antibodies, especially autoimmune diseases such as human systemic lupus erythematosus. The invention also seeks to provide pharmaceutical combinations and compositions suitable for treating such disorders.